Possibilities of dapagliflozin in cardio-reno-metabolic protection in patients with and without type 2 diabetes mellitus


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Abstract

The drugs of the class of sodium-glucose co-transporter type 2 (SGLT-2) inhibitors have been used for a long time as hypoglycemic drugs. The hypoglycemic effect of this class of drugs is based on the predominant selective reversible inhibition of SGLT-2, which leads to a decrease in the reabsorption of glucose and sodium from the glomerular filtrate in the renal tubules, excretion of glucose and sodium in the urine and osmotic diuresis. Dapagliflozin, the first representative of the SGLT-2 inhibitors, which was registered on the territory of the Russian Federation, has been studied in patients with type 2 diabetes mellitus (T2DM) in detail. Further evaluation of the effects of SGLT-2 inhibitors in T2DM patients showed their additional beneficial effect on cardiovascular and renal outcomes. Meta-analysis of three large randomized clinical trials, DECLARE-TIMI58 (dapagliflozin), EMPA-REG OUTCOME(empagliflozin), and CANVAS (canagliflozin), estimating the incidence of cardiovascular and renal outcomes in the pooled population of T2DM patients (n=34,322), has revealed that the use of SGLT-2 inhibitors is associated with a decrease in the relative risk of significant cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, cardiovascular death) by 11%, hospitalization for heart failure by 31% and the progression of renal failure by 45%. In late April 2021, the US Food and Drug Administration (FDA) approved dapagliflozin to reduce the risk of renal and cardiovascular events in patients with chronic kidney disease (CKD) who are at risk of disease progression, regardless of the presence of T2DM. This makes dapagliflozin the first SGLT-2 inhibitor approved for the treatment of CKD in adult patients regardless of diabetic status.

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About the authors

M. B Antsiferov

Endocrinological Dispensary of the Moscow Healthcare Department

Moscow, Russia

O. M Koteshkova

Endocrinological Dispensary of the Moscow Healthcare Department

Moscow, Russia

M. S Novikova

Endocrinological Dispensary of the Moscow Healthcare Department

Moscow, Russia

N. A Demidov

Hospital in Moskovsky town of the Moscow Healthcare Department

Email: nicolay13@mail.ru
Moscow, Russia

References

  1. Tentolouris A., et at. SGLT2 inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects. int J Environ Res Public Health. 2019;16(16):2965. doi: 10.3390/ijerph16162965.
  2. Сайт Государственного реестра лекарственных средств. URL: http://grls.rosminzdrav.ru/GR LS. aspx (дата обращения 11.05.2021).
  3. Kalra S. Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors: A Review of Their Basic and Clinical Pharmacology. Diabetes therapy: research, treatment and education of diabetes and related disorders. 2014;5(2):355-66. doi: 10.1007/s13300-014-0089-4.
  4. Himsworth H.P The relation of glycosuria to glycaemia and the determination of the renal threshold for glucose. Biochem J. 1931;25:1128-46. doi: 10.1042/bj0251128.
  5. DeFronzo R.A., et al. Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nat Rev Nephrol. 2017;13:11-26. Doi: 10.1038/ nrneph.2016.170.
  6. van Baar M.J.B., et al. SGLT2 inhibitors in Combination Therapy: From Mechanisms to Clinical Considerations in Type 2 Diabetes Management. Diabetes Care. 2018;41:1543-56. doi: 10.2337/dc18-0588.
  7. Heerspink H.J., et al. Sodium Glucose Cotransporter inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications. Circulation. 2016;134:752-72. Doi: 10.1161/ CiRCUlATiONAHA.116.021887.
  8. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. Под ред. И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 10-й выпуск. М.: УП ПРИНТ, 2021.
  9. Tang H., et al. Sodium-glucose co-transporter inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: a metaanalysis of randomized controlled trials. Diabetes Obes Metab. 2017;19(1):142-47. Doi: 10.1111/ dom.12785.
  10. Thomas M.C., Cherney D.Z.I. The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure. Diabetologia. 2018;61:2098-207. doi: 10.1007/s00125-018-4669-0.
  11. Vasilakou D., et al. Sodium-glucose 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann intern Med. 2013;159(4):262-74. doi: 10.7326/0003-4819-159-4-201308200 00007.
  12. Инструкция по медицинскому применению лекарственного препарата Форсига (таблетки, покрытые пленочной оболочкой, 5, 10 мг). Регистрационное удостоверение ЛП-002596 от 21.08.2014.
  13. Фадеев В.В. Место ингибитора натрий-глюкозного котранспортера 2-го типа дапаглифлозина в профилактике сердечно-сосудистых осложнений у пациентов с сахарным диабетом 2 типа. Эндокринология: новости, мнения, обучение. 2020;9(2):59-69
  14. Wiviott S.D., et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347-57. Doi: 10.1056/ NEJMoa1812389.
  15. American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2021. Diabetes Care 2021;44(Suppl 1):S111-S124. Doi: 10.2337/ dc21-S009.
  16. Cosentino F., Johansson I., Mellbin L.G., et al. 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41(2):255-323. doi: 10.1093/eurheartj/ehz486.
  17. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2020;98(4S):S1-S115. doi: 10.1016/j.kint.2020.06.019.
  18. McMurray J.J.V, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. Doi: 10.1056/ NEJMoa1911303.
  19. Petrie M.C., et al. Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes. JAMA. 2020;323(14):1353-68. doi: 10.1001/jama.2020.1906. Erratum in: JAMA. 2021;325(13):1335.
  20. Терещенко С.Н. и др. Хроническая сердечная недостаточность. Клинические рекомендации 2020 г. Российский кардиологический журнал. 2020;25:4083. [Tereshchenko S.N., et al. Chronic heart failure. Clinical guidelines 2020. Rossiiskii kardiologicheskii zhurnal. 2020;25:4083. (in Russ.)].
  21. Heerspink H.J.L., et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020; 383(15):1436-46. doi: 10.1056/NEJMoa2024816.
  22. Wheeler D.C., et al. The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics. Nephrol Dial Transplant. 2020;35(10):1700-11. Doi: 10.1093/ ndt/gfaa234.
  23. Wheeler D.C., et al. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021;9(1):22-31. doi: 10.1016/S2213-8587(20)30369-7.
  24. McMurray J.J.V., et al. Effect of Dapagliflozin on Clinical Outcomes in Patients With Chronic Kidney Disease, With and Without Cardiovascular Disease. Circulation. 2021;143(5):438-48. Doi: 10.1161/ CiRCULATiONAHA.120.051675.
  25. URL: https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-chronic-kidney-disease (access date 11.05.2021).
  26. Zannad F., et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020;396(10254):819-29. doi: 10.1016/S0140-6736(20)31824-9.

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